SUBACUTE MEASLES ENCEPHALITIS IN THE YOUNG IMMUNOCOMPROMISED HOST: REPORT OF TWO CASES DIAGNOSED BY PCR AND TREATED WITH RIBAVIRIN AND REVIEW OF THE LITERATURE.
Mustafa MM; Weitman SD; Winick NJ; Bellini WJ; Timmons CF; Siegel JD; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063. Clin Infect Dis, 1993 May, 16:5, 654-60
Two young patients with subacute measles encephalitis are described:
a 20-year-old male hemophiliac infected with human immunodeficiency virus
(HIV) and a 4-year-old girl with acute leukemia. Both patients were afebrile
and had persistent focal seizures and slurred speech beginning 2 and 7
months, respectively, after the onset of uncomplicated acute measles. The
diagnosis of subacute measles encephalitis was established by demonstration
of paramyxovirus nucleocapsid on electron microscopy of brain tissue in
one case and by detection of measles virus genome with the polymerase chain
reaction in both. Treatment of the HIV-infected man with intravenous ribavirin
was begun when the patient lost consciousness after several weeks of seizures;
he died. The girl with leukemia was treated early after the onset of symptoms
and recovered after a 15-week course. Review of 31 previously published
cases revealed a typical clinical presentation. Cerebrospinal fluid
(CSF) analysis, electroencephalography, measurement of measles antibody
in serum and CSF, and computed tomography of the brain were not helpful
in the diagnosis of subacute measles encephalitis. In contrast,
histologic examination of brain tissue proved useful in establishing the
diagnosis. On the basis of our experience and our literature review,
we conclude that histologic and polymerase chain reaction studies of brain
tissue are required for the early diagnosis of subacute measles encephalitis
and that therapy with intravenous ribavirin is effective when administered
early.
SEVERE MEASLES PNEUMONITIS IN ADULTS: EVALUATION OF CLINICAL CHARACTERISTICS AND THERAPY WITH INTRAVENOUS RIBAVIRIN
Forni AL; Schluger NW; Roberts RB; Department of Medicine, Cornell University Medical College, New York, New York 10021. Clin Infect Dis, 1994 Sep, 19:3, 454-62
Between February and April 1991, six adults were admitted to the New
York Hospital because of measles pneumonitis. The diagnosis was confirmed
by serology and/or viral culture. Uncommon clinical features among patients
with this diagnosis included thrombocytopenia, hepatitis, myositis, and
hypocalcemia. All patients were markedly hypoxic (initial alveolar—arterial
oxygen gradients while the patients were breathing room air, 40-61 mm Hg);
four required support with mechanical ventilation. All patients received
therapy with intravenous ribavirin (20-35 mg/[kg.d]) for 1 week. The respiratory
status of five patients (one of whom was positive for human immunodeficiency
virus [HIV]) who were treated early (days 2-5 of illness) promptly improved;
all abnormal parameters eventually returned to baseline. Treatment of the
sixth patient, who was presumed to be HIV-infected, was initiated on hospital
day 22; this patient died of progressive oxygenation failure on day 38.
We conclude that life-threatening measles pneumonitis in adults may be
more common that previously appreciated, regardless of the patient’s immune
status. Therapy with intravenous ribavirin was well tolerated by our
patients and was associated with reversal of respiratory compromise.
RIBAVIRIN INHIBITS VIRAL-INDUCED MACROPHAGE PRODUCTION OF TNF, IL-1, THE PROCOAGULANT FGL2 PROTHROMBINASE AND PRESERVES TH1 CYTOKINE PRODUCTION BUT INHIBITS TH2 CYTOKINE RESPONSE.
Ning Q; Brown D; Parodo J; Cattral M; Gorczynski R; Cole E; Fung L; Ding JW; Liu MF; Rotstein O; Phillips MJ; Levy G; Multiogran Transplant Program, Department of Medicine, Toronto Hospital, University of Toronto, Ontario, Canada. J Immunol, 1998 Apr, 160:7, 3487-93
Ribavirin, a synthetic guanosine analogue, possesses a broad spectrum
of activity against DNA and RNA viruses. It has been previously shown to
attenuate the course of fulminant hepatitis in mice produced by
murine hepatitis virus strain 3. We therefore studied the effects of ribavirin
on murine hepatitis virus strain 3 replication, macrophage production of
proinflammatory mediators including TNF, IL-1, and the procoagulant activity
(PCA), fgl2 prothrombinase; and Th1/Th2 cytokine production. Although
ribavirin had inhibitory effects on viral replication (<1 log), even
at high concentrations complete eradication of the virus was not seen.
In contrast, at physiologic concentrations (up to 500 microg/ml), ribavirin
markedly reduced viral-induced parameters of macrophage activation.
With ribavirin treatment, the concentrations of PCA, TNF-alpha and IL-1beta
all decreased to basal concentrations. Both in vitro and in vivo, ribavirin
inhibited the production of IL-4 by Th2 cells, whereas it did not diminish
the production of IFN-gamma in Th1 cells. In contrast, ribavirin had no
inhibitory effect on TNF-alpha and IL-1beta production in LPS-stimulated
macrophages. These results suggest that the beneficial effects of ribavirin
are mediated by inhibition of induction of macrophage proinflammatory cytokines
and Th2 cytokines while preserving Th1 cytokines.
RIBAVIRIN: A CLINICAL OVERVIEW.
Fernandez H; Banks G; Smith R; Eur J Epidemiol, 1986 Mar, 2:1,
1-14
Ribavirin, a broad spectrum, non-interferon-inducing virustatic chemotherapeutic
agent, demonstrates activity against a wide range of RNA and DNA viruses,
including the retrovirus known to cause the acquired immune deficiency
syndrome. The drug’s proposed mechanism of action, as well as pharmacokinetics
are discussed, and preclinical toxicity, safety and clinical efficacy studies
are presented. To date, the best success has occurred in the use of ribavirin
to treat respiratory syncytial virus infection in infants and young children
and to treat influenza A and B virus infections in young adults. Viral
infections, particularly viral pneumonia, are often life-threatening in
infants with severe combined immunodeficiency disease (SCID), and ribavirin
aerosol has been used successfully to treat respiratory syncytial virus
and parainfluenza virus infection of immunodeficient children. Special
note is taken of ribavirin’s clinical benefit in treating severe and life-threatening
infections caused by the Lassa fever virus and the significant improvement
over either the use of immune plasma or supportive therapy alone. Indeed,
ribavirin thus emerges as the first antiviral drug that is able to reduce
mortality in a highly lethal systemic disease by more than 90%. Additional
studies demonstrate the drug’s efficacy in acute viral hepatitis, herpesvirus
infections, and measles. Controlled clinical trials are underway to
test the drug in patients infected with the AIDS virus.
TOLERANCE AND EFFICACY OF ORAL RIBAVIRIN TREATMENT OF CHRONIC HEPATITIS C: A MULTICENTER TRIAL.
Bodenheimer HC Jr; Lindsay KL; Davis GL; Lewis JH; Thung SN; Seeff LB; Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029-6504, USA. Hepatology, 1997 Aug, 26:2, 473-7
Hepatitis C is a common cause of chronic liver disease that may progress
to cirrhosis. We conducted a multicenter double-blind placebo-controlled
trial of ribavirin 600 mg given orally twice daily for 36 weeks
with follow-up off therapy for an additional 16 weeks. Fifty-nine patients
with compensated chronic hepatitis C were entered. Efficacy was measured
at the end of therapy and after follow-up by normalization of alanine aminotransferase
(ALT), improvement in liver histology, reduction in hepatitis C virus (HCV)
RNA level and improvement of symptoms. Among the ribavirin recipients,
12 of 29 (41.4%) had normal ALT values at 36 weeks compared with only
1 of 30 (3.3%) placebo recipients (P < .001). No patient maintained
a normal ALT when therapy was stopped. No significant decrease in level
of HCV RNA was observed during the study. Histological improvement among
subjects who normalized ALT (-1.67 Knodell index) was significantly greater
than that in other treated patients (+0.33 Knodell index; P < .05).
Fatigue improved in 19.2% of ribavirin-treated subjects and in 8.3%
of placebo recipients whereas no worsening of fatigue was reported by ribavirin
recipients compared with 16.7% of controls. This difference in fatigue
was significant at weeks 36 and 52 (P < .05; .02, respectively). Adverse
events were generally comparable between treatment groups except for a
reversible hemolytic anemia experienced by ribavirin recipients. Chest
pain was noted in four patients on ribavirin. Ribavirin was well tolerated
and improved aminotransferase values and reduced fatigue in patients with
hepatitis C viral infection while treatment was being administered. Because
this action was produced without change in viral level, the mechanism of
action of this agent requires further investigation.
SUBFULMINANT SYNCYTIAL GIANT CELL HEPATITIS: recurrence after liver transplantation treated with ribavirin
François Durand, Claude Degott, Alain Sauvanet, Georges Molas,
Christian Sicot, Patrick Marcellin, JacquesBelghiti, Serge Erlinger, Jean-Pierre
Benhamou and
Jacques Bernuau; Journal of Hepatology, Volume 26 - issue 3( March
1997 ) - page 722 - 726
We report the case of an adult patient affected by acute syncytial giant
cell hepatitis which had a subfulminant course leading to liver transplantation.
Syncytial giant cell hepatitis recurred after transplantation and was efficiently
treated with ribavirin. In this patient, the recurrence of the disease,
the presence of filamentous strands on electron microscopy during both
bouts of hepatitis and the efficacy of ribavirin on post-transplantation
hepatitis suggest that the disease was caused by an original virus. This
observation also suggests that early administration of ribavirin in
patients affected by acute syncytial giant cell hepatitis of unknown origin
could avoid liver transplantation.
A DOUBLE-BLIND, PLACEBO-CONTROLLED EVALUATION OF RIBAVIRIN IN THE TREATMENT OF ACUTE MEASLES.
Uylangco CV; Beroy GJ; Santiago LT; Mercoleza VD; Mendoza SL; Clin Ther, 1981, 3:5, 389-96
In this double-blind, placebo-controlled study, treatment of measles patients with ribavirin resulted in shorter and less severe disease, as well as fewer complications, compared with patients in the placebo, group. Ribavirin was well tolerated. There were no side effects or changes in laboratory values that could be associated with drug-related toxicity. Since reported vaccine failures may increase as immunization levels rise, the use of a safe and effective therapeutic agent, such as ribavirin, will be necessary to treat these cases, as well as those occurring in unvaccinated individuals.